Same Cancer Risk With Two Breast Atypias

Action Points

Both ADH and ALH hyperplasia are associated with increased risk for ductal carcinoma in situ and invasive breast cancers, predominantly ductal, with two-thirds of moderate or high grade.

The ipsilateral breast is at especially high risk for breast cancer in the first 5 years after atypia, with risk remaining elevated in both breasts long term.

A type of breast hyperplasia previously dismissed as a direct cancer precursor preceded invasive breast cancer just as often as a more ominous type of hyperplasia, according to long-term follow-up of 700 women.

Both atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) conferred an identical risk of breast cancer in the same (ipsilateral) breast, and both types of atypia had a 2:1 ratio for the risk of ipsilateral versus contralateral (opposite) breast cancer.

Obtained over a 12.5-year follow-up period, the findings challenge the long-held belief that ADH is a direct precursor of ipsilateral breast cancer whereas ALH is a less specific marker reflecting heightened breast cancer risk in general, as reported online in Cancer Prevention Research.

The findings have implications for management of benign breast disease.

"Most have considered ADH a direct precursor to breast cancer, arguing that it requires complete surgical excision, while others have maintained that ALH serves as an indicator of heightened and equal risk of breast cancer across both breasts and does not need complete surgical removal," Lynn C. Hartmann, MD, of the Mayo Clinic in Rochester, Minn., said in a statement.

"Moreover, some experts have argued that women with atypia develop 'better risk' breast cancers, meaning low-grade cancers with a good prognosis."

Little argument exists that atypical hyperplasia is a high-risk premalignant lesion of the breast. At the same time, incomplete information about the biology of atypical hyperplasia has fueled debate about the risk associated with ADH and ALH, which are found in about 10% of breast biopsies.

The belief that ADH confers a more direct risk of breast cancer has led to different approaches to management of ADH and ALH, even though a paucity of high-quality evidence supports the use of different approaches.

Hartmann and colleagues analyzed data from the Mayo Benign Breast Disease Cohort, the largest longitudinal study of benign breast disease to date. The analysis comprised data on 330 women with ADH, 327 with ALH, and 32 women whose biopsy specimens contained both types of atypical hyperplasia.

Subsequently, 143 of the study participants developed invasive breast cancer.

There were 60 invasive breast cancers in the ADH subgroup (compared with 15 expected among women without atypia), and 75 in the ALH subgroup (versus 16 expected). Seven developed in the women who had both types of tissue abnormalities (two expected) and in one woman the atypia type wasn't specified.

Breast cancer rates did not differ significantly between women with ADH and those with ALH.

In both atypia subgroups, two-thirds of cancers arose in the ipsilateral breast, reflecting the 2:1 ratio traditionally associated only with ADH. Three-fourths of the cancers in the ADH women were invasive and 25% were in situ. In the ALH group, 87% of cancers were invasive and 13% were in situ. Ductal carcinoma accounted for 77% to 78% of cancers in both groups.

About 70% of the cancers in both groups were grade 2 or 3.

The time from benign biopsy to breast cancer diagnosis was within 5 years in 40% of the ADH group and 30.7% of the ALH group. In the ADH group, 31.7% of cancers were diagnosed 6 to 10 years after the benign biopsy, 16.7% at 11 to 15 years, and 11.7% beyond 15 years. In the ALH group, the risk of breast cancer was 23% to 24% at 6 to 10 years, 11 to 15 years, and beyond 15 years.

Three out of 10 (31%) of the ADH group and 21% of the ALH group had node-positive disease at breast cancer diagnosis.

"We found that women with ALH often had higher risk features than those with ADH, including more foci of atypia, younger age, and less complete involution," the authors said of their findings. "In terms of the breast cancers that develop in women with ALH, they are more likely to be invasive, with histologies and grade similar to what is seen in the general population of women.

"Thus, in our view, ALH and ADH both represent important pre-malignant entities."

The large number of patients and long follow-up represent an important contribution to an issue that has not been studied extensively, according to Steven Chen, MD, of City of Hope in Duarte, Calif. Recent clinical guidelines have given more emphasis to the high-risk nature of breast hyperplasia.

"I think this is a reminder that these people have a high enough risk that they should be considered for tamoxifen or raloxifene (Evista)," Chen told MedPage Today.

"I think it's also a reminder that when a physician has a patient with high-risk lesions like this, it's worthwhile to refer them to someone who deals with high-risk breast lesions, someone who can talk about chemoprevention, enhanced screening, and things like that. These lesions take patients out of the standard screening regimen."

UPDATE: This article, originally published Feb. 5, 2014, at 4:32 p.m., was updated with new material (Feb. 5, 2014, at 6:10 p.m.).

Hartmann reported no relevant disclosures. One or more co-authors disclosed relationships with Pfizer.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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